No abstract

Papillary thyroid cancer (PTC) is a predominant type of thyroid cancer. Ionizing radiation is the only well-established risk factor and may result in double-strand breaks. The x-ray repair cross-complementing group 3 (XRCC3) gene plays a vital role in DNA repair through homologous recombination. We aimed at investigating the association between XRCC3 genetic polymorphisms and PTC susceptibility. Eighty-three PTC patients and 367 controls in a Chinese population were enrolled in the study. Tag single-nucleotide polymorphisms (SNPs) were identified by HaploView 4.2 software. Genomic DNAs were isolated from peripheral blood samples by using TaqMan Blood DNA kits. The genotyping of XRCC3 SNPs was performed by TaqMan SNPs genotyping assay. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between XRCC3 SNPs and PTC susceptibility. The statistical analyses were conducted by using SPSS 13.0 software. Four tag-SNPs were initially identified by HaploView 4.2 software. Only one SNP (rs861539) was shown to be significantly associated with increased risk of PTC. There was a significant difference in smoking and drinking status between PTC cases and controls. And the stratified analysis suggested that the polymorphisms of rs861539 in XRCC3 were correlated with PTC risk in the four subgroups of smokers (ex-smokers included), non-smokers, drinkers (ex-drinkers included), and non-drinkers. The meta-analysis showed that only two studies reported a significant association between XRCC3 polymorphisms and PTC risk. In this study, we find a significant association between rs861539 polymorphisms and PTC susceptibility. However, there were inconsistent results in previous published studies. Therefore, further studies in a large population are required to gain insights into the PTC risk conferred by XRCC3 SNPs.

BackgroundThe false negative rate of sentinel lymph node biopsy (SLNB) is 5-10%, and results in improper patient management. The study was to assess the value of ultrasound-suspicious axillary lymph node biopsy (USALNB) in patients with early breast cancer, and to compare SLNB combined with USALNB (SLNB + USALNB) with SLNB alone.MethodsFrom January 2010 to July 2013, 216 patients with early breast cancer were enrolled consecutively at the Department of Breast and Thyroid Surgery, Qianfoshan Hospital, Shandong University. All patients underwent wire localization of the suspicious node by color Doppler ultrasonography, followed by SLNB 2–3 hours later, suspicious node lymphadenectomy, and level ≥ II axillary dissection (as the gold standard). The predictive values of node status between SLNB + USALNB and SLNB alone were compared.ResultsThe success rate of SLNB was 99.1% (214/216). After axillary dissection, 71 patients were confirmed with axillary lymph node metastases by pathological examinations. Eight false negatives were observed using SLNB alone, resulting in sensitivity of 88.7%, specificity of 100%, false negative rate of 11.3%, and false positive rate of 0% in predicting the axillary node status. SLNB + USALNB resulted in sensitivity of 97.2%, specificity of 100%, false negative rate of 2.8%, and false positive rate of 0%. The false negative rate of SLNB + USALNB was significantly different from that of SLNB alone (P = 0.031).ConclusionsSLNB + USALNB seems to be a low-risk procedure that might be useful in reducing the false negative rate of SLNB, improving the accuracy of axillary nodes evaluation in early breast cancer.

Resistance to trastuzumab is frequently observed during the treatment of patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancers. The aim of the present study was to determine if the phosphorylated proline-rich Akt substrate of 40 kDa (phospho-PRAS40Thr246), a novel biomarker for phosphoinositol-3 kinase (PI3K) pathway activation, could predict the response of HER2-positive metastatic breast cancers to treatment with trastuzumab. Formalin-fixed, paraffin-embedded tumor tissue samples were retrospectively collected from 55 trastuzumab-treated patients. Next, the expression of phospho-PRAS40Thr246 and phosphatase and tensin homolog (PTEN) was assessed by immunohistochemistry. In total, five common phosphoinositol-3 kinase α catalytic subunit mutations, namely E542K, E545K, E545D, H1047R and H1047L, were identified by the amplification-refractory mutation system, using the allele-specific polymerase chain reaction. The activation of the PI3K pathway, as determined by low PTEN expression or the presence of oncogenic PIK3CA mutations, was observed in 49.1% (27 cases) of the 55 HER2-positive metastatic breast cancer tissues. In total, 40% of the tumors were defined as being phospho-PRAS40Thr246-positive. Furthermore, the results revealed that phospho-PRAS40Thr246 expression was associated with the PI3K pathway activation status and an increased risk of tumor progression in HER2-positive metastatic breast cancer patients who had received trastuzumab-based therapy. Therefore, phospho-PRAS40Thr246 expression levels may reflect the PI3K pathway activation status and act as a biomarker for HER2-amplified breast cancer patients who are unlikely to respond to trastuzumab-based therapy.